One theory which has played a dominant role in our thinking postulates that aging is related to the effects of long term histoincompatibility reactions arising in the body. This reaction may be due to a loss of regulatory control by specific T-cell subpopulations. Loss of regulatory cells (suppressor cells) may result from accelerated senesence of the precursor of these cells or inability of the precursors to differentiate into active suppressors because of some defect in the milieu of the aging animal. Such loss of suppressor cell regulation may allow forced maturation of the antigen reactive effector populations. We have observed that thymus cell in vitro express receptors which can react with autologous, allogeneic and, in some instances, xenogeneic erythrocytes. We initially hypothesized that such cells may play a major role as the precursors of effector cells in initiating histoincompatibility reactions giving rise to autoimmune diseases. On the contrary, our evidence now suggests this subpopulation of T-cells may provide regulatory control to inhibit the autoimmune hemolytic antibody production in NZB mice. These cells have been characterized as phi ion, cortisone sensitive, T1 cells and appear to belong to the population described by Weksler et al. (Cellular Immunology 14:98, 1974) which plays a suppressive role in antigenic competition. Our long range objective is to understand what controls immunosenesence of the immune system and to develop means to reconstitute or re-establish regulatory control of an aging immune system. To do this study, three mouse strains are being investigated simultaneously: the short-lived auto-immune prone NZB, the non-autoimmune prone Balb/c, and the long-lived C57BL. BIBLIOGRAPHIC REFERENCES: Ghanta, V.K., Davis, D.A. and Hiramoto, R.N., Age Related Changes in Autologous Erythrocyte T-Rosettes. Fed. Proc. 36:1246, 1977. Hiramoto, R.N. and Ghanta, V.K. Histocompatibility Antigens in Immunochemistry of Proteins. Edited by M.Z. Atassi. pp. 401-439, 1977, Plenum Press, New York.